To investigate the consequences of ectopic expression of interferon gamma (IFN-gamma) in the lens and how this lymphokine growth factor may influence the fate of cells committed to a particular differentiation state, we used the murine alphaA-crystallin promoter (alphaACry) to direct the expression of IFN-gamma to the lens of transgenic mice. Two transgenic mouse lines were established using two distinct strains, Balb/c and FVB/N. In both the alphaACry-IFN-gamma/Balb/c and alphaACry- IFN-gamma/FVB/N transgenic mice, the essential histopathological features observed were very similar at all developmental of ocular tissues of these mice resulted from alphaACry-IFN-gamma expression. Recently we have generated transgenic rats using the alphaACry-IFN-gamma cDNA construct, making our transgenic rats the first transgenic rats to be generated at the National Institutes of Health. Constitutive expression of IFN-gamma in the lens induced ocular pathology and aberrant major histocompatibility complex (MHC) class-II protein synthesis in several ocular tissues. These transgenic mice and rats provide powerful models for understanding the molecular pathways governing synchronized programmed differentiation of ocular tissues and for studying the linkage between aberrant MHC expression and predisposition to autoimmune diseases.